Involvement of PLAGL2 in activation of iron deficient- and hypoxia-induced gene expression in mouse cell lines
Involvement of PLAGL2 in activation of iron deficient- and hypoxia-induced gene expression in mouse cell lines
复制标题
DOI：
10.1038/sj.onc.1204647
复制
发表时间：
2001-08-02
期刊：
影响因子：
8
通讯作者：
Taketani, S
中科院分区：
文献类型：
--
作者：
Furukawa, T;Adachi, Y;Taketani, S
我们寻找缺铁诱导的cDNA，使用减法克隆和mRNA从去铁胺处理的小鼠巨噬细胞Raw 264.7细胞。我们发现了一个多形性腺瘤基因2（PLAGL 2），PLAG超家族蛋白表现出抗肿瘤细胞增殖特性之一。小鼠PLAGL 2由496个氨基酸组成，具有7个C2 H2锌指。去铁胺可诱导RAW264.7细胞、小鼠红白血病细胞和Balb/c 3 T3细胞PLAGL 2 mRNA的表达。缺氧也使PLAGL 2 mRNA表达增加。PLAGL 2在COS-7细胞中的表达导致核定位。PLAGL 2具有与富含GC的寡核苷酸的潜在结合能力，并在瞬时报告基因测定中激活具有结合序列的基因的转录，这一发现与PLAGL 2同源物ZAC-1中观察到的情况一致。瞬时共转染PLAGL 2或ZAC 1 cDNA和含有乳酸脱氢酶A（LDHA）启动子携带缺氧诱导因子-1应答元件的报告基因导致Balb/c 3 T3和HepG 2细胞中基础转录的增加。当PLAGL 2表达时，通过去铁胺处理或缺氧增加的LDHA启动子的转录激活进一步增强。我们提出PLAGL 2通过调节铁耗竭或缺氧诱导的基因表达参与肿瘤细胞的细胞周期阻滞和凋亡。
We searched iron-deficient inducible cDNA, using subtraction cloning and mRNA from desferrioxamine-treated mouse macrophage Raw264.7 cells. We identified a pleomorphic adenoma gene like 2 (PLAGL2), one of PLAG superfamily proteins exhibiting antiproliferative properties on tumor cells. Mouse PLAGL2 consists of 496 amino acids with seven C2H2 zinc-fingers. PLAGL2 mRNA was induced in RAW264.7 cells, mouse erythroleukemia cells and Balb/c 3T3 cells when they were treated with desferrioxamine. Hypoxia also increased PLAGL2 mRNA. Expression of PLAGL2 in COS-7 cells led to nuclear localization. PLAGL2 had potential binding ability to GC-rich oligonucleotide and activated transcription of a gene with the binding sequence in transient reporter assay, a finding consistent with a case seen in a PLAGL2 homolog, ZAC-1. Transient co-transfection of PLAGL2 or ZAC1 cDNA and a reporter containing a lactate dehydrogenase A (LDHA) promoter carrying the hypoxia inducible factor-1 responsive element led to an increase in the basal transcription in Balb/c 3T3 and HepG2 cells. Activation in transcription from the LDHA promoter increased by desferrioxamine treatment or hypoxia was further enhanced when PLAGL2 was expressed. We propose that PLAGL2 is involved in the cell cycle arrest and apoptosis of tumor cells by regulating iron depletion- or hypoxia-inducible gene expression.